Poly(lactic-co-glycolic acid) (PLGA) has garnered considerable attention as a versatile platform for the delivery of active pharmaceutical ingredients (APIs). In the field of API delivery, the glass transition temperature (T_g) is widely recognized as a fundamental predictor of drug release kinetics from PLGA formulations. Despite making significant progress in understanding the qualitative trends and general effects of multiple molecular parameters on the glass transition properties of PLGA, accurately predicting the T_g value of a PLGA with a specific molecular weight and composition remains a challenge. One factor that has previously been overlooked is the contribution of statistical monomer sequence distribution to the T_g of PLGA. To address this research gap, we employed a novel Feed Rate-Controlled Polymerization (FRCP) technique to synthesize PLGA homopolymers with a comparable molecular weight and varying degrees of repeat unit (lactate (L, repeat unit A) and glycolate (G, repeat unit B)) sequence uniformity (uniform vs gradient PLGA) at different monomer compositions (lactide/glycolide (LA/GL) ratios). This allowed us to systematically investigate the effect of LA/GL sequence distribution on the glass transition properties of PLGA. We observed a significant negative deviation (<∼8 K) from the predictions of the Fox equation in the T_g vs copolymer composition plot, suggesting the presence of a repulsive interaction between the LA and GL monomers. The experimental T_g data and the measures of monomer sequence length obtained in our study exhibited quantitative agreement with the predictions of both the Johnston theory (based on the free volume concept) and the Barton theory (based on the configurational entropy concept). Based on our findings, we propose that by considering the copolymer composition and monomer dyad/triad distribution, it is possible to reasonably predict the T_g of a PLGA material using the alternating dyad or tetrad glass transition values (T_gAB or T_gAABB, respectively) obtained in our study, without the need for adjustable parameters.

中文翻译：

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单体序列分布对聚(d,l-乳酸-乙醇酸) (PLGA) 玻璃化转变温度的影响


聚乳酸-乙醇酸 (PLGA) 作为一种用于输送活性药物成分 (API) 的多功能平台而受到广泛关注。在 API 输送领域，玻璃化转变温度 (T _g ) 被广泛认为是 PLGA 制剂药物释放动力学的基本预测因子。尽管在理解多个分子参数对 PLGA 玻璃化转变特性的定性趋势和一般影响方面取得了重大进展，但准确预测具有特定分子量和组成的 PLGA 的 T _g 值仍然是一个挑战。以前被忽视的一个因素是统计单体序列分布对 PLGA 的 T _g 的贡献。为了解决这一研究空白，我们采用了一种新颖的进料速率控制聚合 (FRCP) 技术来合成具有相当分子量和不同程度重复单元（乳酸（L，重复单元 A）和乙醇酸酯（G，重复单元）的 PLGA 均聚物B)) 不同单体组成（丙交酯/乙交酯 (LA/GL) 比例）下的序列均匀性（均匀与梯度 PLGA）。这使我们能够系统地研究 LA/GL 序列分布对 PLGA 玻璃化转变特性的影响。我们在 T _g 与共聚物组成图中观察到与 Fox 方程的预测存在显着的负偏差 (<∼8 K)，这表明 LA 和 GL 单体之间存在排斥相互作用。我们研究中获得的实验 T _g 数据和单体序列长度的测量结果与 Johnston 理论（基于自由体积概念）和 Barton 理论（基于构型熵的概念）。 基于我们的研究结果，我们建议通过考虑共聚物组成和单体二元组/三元组分布，可以使用交替二元组或四元组玻璃化转变值（T _gAB 或 T _gAABB 分别在我们的研究中获得，无需可调参数。